Prion diseases are neurodegenerative disorders that appear to be due to a conformational change, involving the conversion of alpha-helices in the normal, cellular isoform of the prion protein (PrP^C) to beta-structure in the infectious scrapie form (PrP^Sc). Prion diseases include BSE (Mad-Cow disease), Scrapie (in sheep), and CJD, GSS, and FFI in humans. We seek to understand the structural conversion between PrP^C and PrP^Sc and the mechanism of infectivity of PrP^Sc. To understand these conformational changes in the prion protein, we are using a complete battery of computational techniques. These techniques range from all-atom molecular dynamics simulations, providing the atomic level detail, to gene homology and secondary structure prediction studies.